Signal Transduction via the Mitogen-activated Protein Kinase Pathway Induced by Binding of Coagulation Factor VIIa to Tissue Factor
| Autor: | Mirella Ezban, Ole Thastrup, Donald C. Foster, Lars Christian Petersen, Nana Jacobsen, Brit B. Sørensen, Nils C.H. Bergenhem, Lars Kongsbak Poulsen, James D. Kelly |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
MAPK/ERK pathway
Factor VIIa Biology Kidney Biochemistry Thromboplastin Tissue factor Dogs Genes Reporter Cricetinae Animals Phosphorylation Molecular Biology Cells Cultured Flavonoids Mitogen-Activated Protein Kinase 3 Kinase Cell Biology Transfection Factor VII Molecular biology Recombinant Proteins Gene Expression Regulation Mitogen-activated protein kinase Calcium-Calmodulin-Dependent Protein Kinases Factor X Factor Xa STAT protein biology.protein Mitogen-Activated Protein Kinases Signal transduction Protein Binding Signal Transduction |
| Zdroj: | Journal of Biological Chemistry. 273:6228-6232 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.273.11.6228 |
| Popis: | The putative role of tissue factor (TF) as a receptor involved in signal transduction is indicated by its sequence homology to cytokine receptors (Bazan, J. F. (1990) Proc. Natl. Acad. Sci. U. S. A. 87, 6934-6938). Signal transduction induced by binding of FVIIa to cells expressing TF was studied with baby hamster kidney (BHK) cells stably transfected with TF and with a reporter gene construct encoding a luciferase gene under transcriptional control of tandem cassettes of signal transducer and activator of transcription (STAT) elements and one serum response element (SRE). FVIIa induced a significant luciferase response in cells expressing TF, BHK(+TF), but not in cells without TF. The BHK(+TF) cells responded to the addition of FVIIa in a dose-dependent manner, whereas no response was observed with active site-inhibited FVIIa, which also worked as an antagonist to FVIIa-induced signaling. Activation of the p44/42 MAPK pathway upon binding of FVIIa to TF was demonstrated by suppression of signaling with the specific kinase inhibitor PD98059 and demonstration of a transient p44/42 MAPK phosphorylation. No stimulation of p44/42 MAPK phosphorylation was observed with catalytically inactive FVIIa derivatives suggesting that the catalytic activity of FVIIa was obligatory for activation of the MAPK pathway. Signal transduction caused by a putative generation of FXa activity was excluded by experiments showing that FVIIa/TF-induced signaling was not quenched by tick anticoagulant protein, just as addition of FXa could not induce phosphorylation of p44/42 MAPK in BHK(+TF) cells. These results suggest a specific mechanism by which binding of FVIIa to cell surface TF independent of coagulation can modulate cellular functions and possibly play a role in angiogenesis and tumor metastasis as indicated by several recent observations. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|